The early termination was NOT due to safety reasons, terminated because of the very slow recruitment and problematic access to the study medication in Europe

Uterine sarcomas are rare tumors with a poor prognosis.

The main purpose of this phase II proof-of-principle- pilot study is to test the efficacy of the hydroxamic acid-based Histone deacetylase inhibitor (HDACI) Vorinostat (SAHA) as monotherapy in patients with HDAC-positive, progressive, metastatic uterine sarcomas and mixed epithelial and mesenchymal tumors after prior anti-proliferative therapy.

This is an open-label, single arm, proof of concept-study of the HDAC-inhibitor vorinostat in patients with refractory uterine sarcoma that have been pre-tested for an high expression of HDAC. Patients will receive Vorinostat, 400 mg (4 capsules á 100mg of Zolinza) orally once daily for the first 14 days of a 21 day cycle. Treatment will be continued for 4 cycles (treatment period 1). Patients with a response or stable disease after 4 cycles as determined by computed tomography (CT) of target an non target-lesions will be continued on vorinostat therapy at the tolerated schedule and dosage until disease progression, unacceptable toxicity or patients' withdrawal of the consent. At the maximum, a total of 12 cycles will be administered over a 9 months period (treatment periods 2 and 3).

Inclusion Criteria:

• Histologically confirmed metastatic uterine sarcoma (endometrial stromal sarcoma, undifferentiated uterine sarcoma, leiomyosarcoma, adenosarcoma and carcinosarcoma

  • High HDAC-positivity of the tumor determined by immunohistochemistry
  • Patients must have received prior systemic antineoplastic therapy
  • Patient is not amenable for curative therapy
  • Age >= 18 years
  • Estimated life expectancy > 3 months
  • Measurable disease on CT/MRI (at least one measurable lesion >1cm) or chest X-ray (at least one measurable lesion >2cm)
  • Karnofsky performance status of 60-100
  • Adequate hematologic, renal and hepatic function
  • Subject is able to swallow and retain oral medication and does not have uncontrolled emesis
  • No fertility preserved
  • Written informed consent

Exclusion Criteria:

• Lack of or low expression of HDAC (see 4.1 "Pre-Screening")

  • Significant cardiac disease
  • Other invasive malignant tumor diagnosed within the last 5 years (e.g. metastases from breast cancer in the last 3 years)
  • Significant bowel obstruction
  • Severe uncontrolled infection
  • Known HIV-positivity
  • Symptomatic brain metastasis or leptomeningeal disease
  • Pre-existing significant liver disease, severe hepatic impairment (Bilirubin no greater than 1.5 times upper limit of normal (ULN) and/or aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) greater than 2.5 times ULN)
  • Known history of allergic reaction to vorinostat or similar medications
  • Systemic therapy or an investigational agent within 21 days prior to study inclusion
  • Uncontrolled hypertension (sustained systolic blood pressure > 150 mmHg or diastolic pressure > 100 mmHg despite optimal medical management)
  • Major surgery within 3 weeks of enrollment when diagnosed at an early stage
  • Symptomatic congestive heart failure
  • Unstable angina pectoris or cardiac arrhythmia
  • Myocardial infarction within last 6 months
  • Known active hepatitis B or hepatitis C
  • Psychiatric illness/social situations that would limit compliance with study requirements-
  • Prior history of thrombotic or thromboembolic events, unless adequately controlled by anticoagulant therapy

The investigated condition occurs exclusively in women

Statistical evaluation was not possible as only 1 Patient reached end point 1.

From enrolment to study completion per Patient, up to 41 weeks.